Oh Woong Kwon

Incidence and clinical patterns of polypoidal choroidal vasculopathy in Korean patients.

PurposeTo determine the incidence, demographic features, and clinical characteristics of polypoidal choroidal vasculopathy (PCV) in Korean patients.MethodsA retrospective review was undertaken of 392 eyes of 321 symptomatic patients suspected of having exudative age-related macular degeneration (AMD) after their first visit to a tertiary hospital between February 2002 and May 2006. All patients underwent a complete ophthalmic examination, including fluorescein and indocyanine green angiography (ICGA).ResultsOf the 321 patients (392 eyes), 79 (98 eyes, 24.6%) were diagnosed with PCV. The mean PCV patient age was 64.6 ± 7.6 years. PCV was more common in men (78.5%), and was usually unilateral (75.9%). In terms of PCV clinical manifestation, 52% of patients showed an exudative pattern, 34.7%, a hemorrhagic pattern, and 13.3%, an extensive hemorrhagic pattern. The mean visual acuity at presentation was 0.231 ± 0.256. Classification was based on ICGA findings; 52% of patients showed relatively large aneurismal dilations, 25.5% showed atypical vessel deformations, and 22.5% showed dense clusters of numerous small hyperfluorescent dots.ConclusionsThe incidence of PCV in Korean exudative AMD patients was relatively high compared with that in other ethnic groups. As in other Asian patient populations, PCV occurred more commonly in men and was predominantly unilateral.

Problems Associated with the 25-Gauge Transconjunctival Sutureless Vitrectomy System during and after Surgery

Objective: To report the initial experiences with the 25-gauge transconjunctival sutureless vitrectomy (TSV) system, including intraoperative and postoperative problems. Methods: We retrospectively reviewed the medical records and surgical videotapes of 50 consecutive patients who underwent vitrectomy performed by one surgeon using the TSV system. Results: Intraoperatively, we encountered such problems as difficulty in inserting the microcannula, which led to deformity, instability of the microcannula, self-disconnection of the infusion tip and resultant lens damage, and conversion to 20-gauge conventional vitrectomy. Postoperatively, there were 8 cases with hypotony (IOP < 6 mm Hg) on day 1, 6 cases with elevated IOP, and 3 cases with retinal detachment during follow-up. Conclusion: Though certain problems exist during and after surgeries using TSV, this system is both convenient and safe for various vitreoretinal procedures.

Photodynamic therapy with verteporfin for polypoidal choroidal vasculopathy of the macula.

Purpose: Indications for photodynamic therapy (PDT) have increased from age-related macular degeneration with choroidal neovascularization (CNV), containing more than 50% of the classic component, to occult CNV, myopic CNV and CNV due to ocular histoplasmosis syndrome. In the present study, the effect of PDT with verteporfin was examined in polypoidal choroidal vasculopathy (PCV) of the macula. Methods: PDT was performed in 9 eyes with PCV of the macula. Fundus examination, fluorescein angiography, and indocyanine green angiography were performed before PDT and 3 months after PDT in all eyes. Optical coherence tomography was performed in 6 eyes. Results: After the initial PDT, visual acuity was stabilized or improved in 8 eyes (89%), polypoid elements were obliterated in 7 eyes (78%), and vascular nets were reduced in 8 eyes (89%). Of 6 eyes that received optical coherence tomography, pigment epithelium detachment was reduced or disappeared in all eyes except 1, which developed a disciform scar. An additional PDT was performed in 4 eyes to decrease vascular leakage. During the follow-up period of 3–18 months, no reactivation of PCV was observed. Conclusion: PDT offers an effective way of treating PCV of the macula, by obliterating polypoid elements of the PCV. However, long-term follow-up is needed.

Concentration of cytokines in the aqueous humor of patients with naive, recurrent and regressed CNV associated with amd after bevacizumab treatment.

Purpose: To evaluate the concentration of various cytokines in the aqueous humor of patients with naive, recurrent, and regressed choroidal neovascularization (CNV) of age-related macular degeneration after bevacizumab treatment. Methods: Aqueous humor samples were collected from 36 eyes with age-related macular degeneration and 10 controls during cataract surgery. Of 36 patients with age-related macular degeneration, 5 eyes were naïve to bevacizumab injection, 14 eyes had recurrent CNV after bevacizumab treatment, and 17 eyes had regressed CNV after bevacizumab treatment. Cytokines were measured by an immunoassay using multianalyte biochip array technology (Evidence investigator cytokine and growth factor biochip array, RANDOX laboratories Ltd., Crumlin, UK). Results: No significant difference in the cytokine levels was noted between the control group and the naïve CNV group (all P > 0.05). Vascular endothelial growth factor in both naive (66.8 ± 35.1 pg/mL) and recurrent CNV groups (55.7 ± 63.0 pg/mL) was significantly higher compared with regressed CNV group (9.8 ± 12.8 pg/mL, P = 0.025 and P = 0.004, respectively) but was not statistically different from the control group (81.8 ± 43.7 pg/mL, P = 0.310 and P = 0.212, respectively). The aqueous humor level of tumor necrosis factor-&agr; and interleukin (IL)-2 was significantly lower in recurrent CNV group (P = 0.036 and P = 0.019) compared with the control group. In the active CNV patients (recurrent and naïve CNV groups), the aqueous humor levels of IL-6 and IL-8 significantly correlated with the size of CNV (&rgr; = 0.692, P = 0.001 and &rgr; = 0.745, P < 0.001, respectively). Conclusion: Levels of Vascular endothelial growth factor measured in the aqueous humor were significantly related to the disease activity of CNV in age-related macular degeneration. Moreover, IL-2, IL-6, IL-8, and tumor necrosis factor-&agr; may be related to the activity of CNV.

Vascular Endothelial Growth Factor as an Autocrine Survival Factor for Retinal Pigment Epithelial Cells under Oxidative Stress via the VEGF-R2/PI3K/Akt

PURPOSE Vascular endothelial cell growth factor (VEGF) is strongly induced by oxidative stress in retinal pigment epithelial (RPE) cells, and VEGF-A is a survival factor for various cell types. This study was conducted to determine whether the autocrine VEGF signaling pathway in RPE cells is involved in the mechanism of adaptive response to oxidative stress. METHODS ARPE-19 cells were treated with hydrogen peroxide, and cell death was measured by flow cytometry with annexin V-fluorescein isothiocyanate. Survival analysis was performed with pretreatment of VEGF-A-neutralizing antibodies, VEGF receptor tyrosine kinase inhibitor (SU5416), or VEGF-A receptor-neutralizing antibodies (anti-VEGF-R1 and anti-VEGF-R2). The expression of VEGF-A, -R1, -R2, and soluble VEGF-R1 was determined by semiquantitative RT-PCR or Western blot analysis. Phosphorylation of VEGF-R2 was detected with immunoprecipitation and immunoblot analysis. RESULTS Hydrogen peroxide-induced cell death was promoted by pretreatment with VEGF-A and anti-VEGF-R2-neutralizing antibodies, but not with anti-VEGF-R1-neutralizing antibody. Phosphorylation of VEGF-R2 in RPE cells was induced by hydrogen peroxide, and pretreatment with anti-VEGF-A-neutralizing antibody inhibited phosphorylation. Phosphorylation of Akt under oxidative stress was abrogated by pretreatment with neutralizing antibodies against either VEGF-A or SU5416. CONCLUSIONS Autocrine VEGF-A enhanced RPE cell survival under oxidative stress; the autocrine VEGF-A/VEGF-R2/PI3K/Akt pathway is involved. Neutralization of VEGF-A signaling, as in eyes with age-related macular degeneration, may influence RPE cell survival.

Intravitreal bevacizumab injection for central serous chorioretinopathy.

Purpose: The purpose of this study was to evaluate the effectiveness of intravitreal injection of bevacizumab for treatment of central serous chorioretinopathy. Methods: In this retrospective case series, six patients (six eyes) with central serous chorioretinopathy were treated with an intravitreal injection of bevacizumab. The outcome measures included visual acuity with Early Treatment Diabetic Retinopathy Study letters, central macular thickness measurement with optical coherence tomography, changes in fluorescein angiography, and indocyanine green angiography. Results: The mean age of the patients was 42.3 years and the mean follow-up period was 9.0 months (range, 5–12 months). Mean visual acuity ± standard deviation increased from 40.8 ± 8.3 Early Treatment Diabetic Retinopathy Study letters at baseline to 49.0 ± 5.0 Early Treatment Diabetic Retinopathy Study letters at 1 month (P = 0.046) and to 53.3 ± 5.2 Early Treatment Diabetic Retinopathy Study letters at 3 months (P = 0.028). Mean central macular thickness ± standard deviation decreased from 331.5 ± 93.4 &mgr;m to 164 ± 34 &mgr;m at 3 months (P = 0.043). Leakage on fluorescein angiography and hyperpermeability on indocyanine green angiography decreased in conjunction with improvement in central macular thickness observed by optical coherence tomography. Conclusion: Intravitreal bevacizumab injections resulted in improved visual acuity and anatomical results for central serous chorioretinopathy.

Association between Complement Factor H Gene Polymorphisms and Neovascular Age-Related Macular Degeneration in Koreans

PURPOSE This study was undertaken to investigate the association between the complement factor H (CFH) gene and exudative age-related macular degeneration (AMD) in Korean patients. METHODS Genomic DNA was isolated from the peripheral leukocytes of patients with exudative AMD (n = 114) and control subjects (n = 187). The sole criterion for exudative AMD was the presence of choroidal neovascularization. Four single-nucleotide polymorphisms (SNPs: -275C>T, I62V, Y402H, and IVS15) located in promoter, exon 2, exon 9, and intron 15 of the CFH gene were genotyped by PCR-based direct sequencing. RESULTS The frequency of the C allele of Y402H (AMD, 10.5%; control, 6.5%) was found to be lower in Koreans than in Caucasians. In the present study, the difference between the frequencies of Y402H in cases and control subjects did not reach statistical significance (P = 0.071). However, the frequencies of the major alleles of three SNPs (-275C>T, I62V, and IVS15) were significantly different in patients and control subjects, and these SNPs were found to be separately associated with an elevated risk of exudative AMD. Seven haplotypes were identified in Koreans. Haplotype analysis showed that two haplotypes (TGTG, CGTG) conferred significantly higher risks of exudative AMD (P = 0.013, 0.035), and one haplotype (CATA) was significantly protective (P < 0.001). CONCLUSIONS In Korean subjects, CFH polymorphism appears to be a considerable hereditary contributor to exudative AMD. Y402H polymorphism which has been suggested to be a major risk factor of AMD in Caucasians was found to be only marginally associated with exudative AMD with low frequency, whereas three adjacent SNPs in the CFH gene were significantly associated with AMD in Koreans.

Effects of macular ischemia on the outcome of intravitreal bevacizumab therapy for diabetic macular edema.

Purpose: To evaluate the effects of macular ischemia on visual outcomes in patients with diabetic macular edema (DME), after intravitreal bevacizumab injections. Methods: Data on 59 eyes of 53 consecutive patients treated with intravitreal bevacizumab for DME were retrospectively reviewed. Data from preoperative fluorescein angiography (FA) tests were examined. Patients with an enlarged foveal avascular zone (FAZ), ≥1000 &mgr;m, or a broken perifoveal capillary ring at the border of the FAZ, with a distinct area of capillary nonperfusion within one disk diameter of the foveal center in the transit phase of fluorescein angiography, were defined as having macular ischemia. The patients were thus divided into two groups: with or without macular ischemia. Early Treatment Diabetic Retinopathy Study (ETDRS) scores, and foveal thicknesses measured using third generation ocular coherence tomography (OCT), were evaluated at baseline and at 1 month and 3 months after treatment. Results: At 3 months after treatment, the mean visual acuity (VA) score decreased from a baseline VA of 0.52 ± 0.27 (approximate Snellen equivalent, 20/63) to 0.57 ± 0.21 (20/80) in the ischemic group. In the nonischemic group, by contrast, the VA improved from 0.66 ± 0.34 (20/100) at baseline to 0.59 ± 0.33 (20/80) at 3 months post-treatment. Nine of 18 eyes (50%) in the ischemic group, but only 9 of 41 eyes (21%) in the nonischemic group, experienced visual losses of ≥1 line on the ETDRS chart (P = 0.031, Pearson chi-square test). Four eyes (22%) in the ischemic group, but only 2 eyes (5%) in the nonischemic group, lost ≥3 lines (P = 0.042, Pearson chi-square test). Conclusion: Macular ischemia may have a negative effect on short term visual outcomes after intravitreal bevacizumab injections in patients with DME.

Effect of intravitreal bevacizumab injection on aqueous humor cytokine levels in clinically significant macular edema.

PURPOSE To determine the effect of intravitreal bevacizumab (Avastin, Genentech, Inc., San Francisco, CA) injection on aqueous humor cytokine levels in clinically significant macular edema (CSME). DESIGN Retrospective, comparative study. PARTICIPANTS Seventeen eyes undergoing intravitreal injection for CSME and 11 eyes undergoing cataract surgery as negative controls. Nine patients with CSME were naïve to intravitreal bevacizumab injection (CSME group 1), and 8 patients previously received 1 intravitreal bevacizumab injection at a mean of 9.6+/-1.4 weeks earlier (CSME group 2). METHODS Aqueous humor samples were collected before performing intravitreal injection in the CSME group and during cataract surgery in the control group. Aqueous cytokine levels were determined by immunoassay using multianalyte biochip array technology. MAIN OUTCOME MEASURES The concentration of cytokines in the aqueous humor was recorded as a mean (+/- standard deviation) in CSME groups 1 and 2 and the control group. Correlations of aqueous humor cytokine levels were evaluated. RESULTS Significantly higher levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were noted in patients with CSME compared with controls. Although higher vascular endothelial growth factor (VEGF) levels were noted in CSME group 1 (P = 0.001), a lower level of VEGF was noted after intravitreal bevacizumab injection in CSME group 2 (P = 0.004) compared with the control group. VEGF levels were also lower in CSME group 2 compared with CSME group 1 (P = 0.001). In CSME group 2, a significant negative correlation was observed between VEGF and IL-6 (rho = -0.833, P = 0.01) and VEGF and MCP-1 (rho = -0.736, P = 0.037). CONCLUSIONS Significantly higher levels of IL-6, IL-8, VEGF, and MCP-1 were noted in the aqueous humor of CSME. However, recurrence of macular edema was noted with significantly lower concentrations of VEGF after a single intravitreal injection of bevacizumab. This suggests the potential importance of IL-6 and MCP-1 in the pathogenesis of CSME. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Foveal ganglion cell layer damage in ischemic diabetic maculopathy: correlation of optical coherence tomographic and anatomic changes.

PURPOSE To describe the morphologic features of ischemic diabetic maculopathy by high-resolution optical coherence tomography (OCT) and their correlation with the damaged foveal avascular zone (FAZ) on fluorescein angiography (FA). DESIGN Observational case series. PARTICIPANTS One hundred twenty-four eyes of 63 patients with diabetic retinopathy and acceptable FA and OCT images were studied. Twenty-three normal fellow eyes of 23 nondiabetic patients with unilateral acute central serous choroidopathy also were studied. METHODS High-speed Fourier-domain OCT was used with a speckle noise-reduction technique to obtain detailed horizontal and vertical images through the center of the fovea and horizontal raster scans every 100 microm. Foveal ganglion cell layer (GCL) damage was identified on OCT as an evident difference in foveal thickness and contour compared with a normal fovea or as asymmetry within the fovea. Fluorescein angiography was performed by confocal scanning laser ophthalmoscope (HRA 2; Heidelberg Engineering, Heidelberg, Germany), and FAZ damage visible during the FA arterial phase was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) FA grading system. Correlations were sought between foveal GCL damage identified on OCT and FA capillary dropout sites. MAIN OUTCOME MEASURES Foveal GCL damage on OCT, the size of the foveola on OCT (defined as the area of GCL thickness <10 microm), ETDRS grading of FAZ on FA, and visual acuity. RESULTS Among the 124 eyes with diabetic retinopathy, 62 (50%) had FA evidence of either FAZ damage higher than grade 1 or FAZ capillary loss. In these eyes, damage to the FAZ seen on FA also could be detected on OCT (positive predictive value, 84.5%; negative predictive value, 72.9%), and locations of FAZ damage seen on FA corresponded well with sites of foveal GCL damage on OCT. In nondiabetic, normal eyes, the size of the foveola on OCT matched the size of the FAZ on FA. CONCLUSIONS Evidence of foveal GCL damage on OCT is a good indicator of macular ischemic damage in eyes with diabetic retinopathy. Although in this study FA was more sensitive than OCT in detecting vascular damage, OCT provides objective results and seems to be a good noninvasive substitute for FA.